Chemical process

ABSTRACT

A process for the preparation of 3,5-dichloropyridine comprising reacting a trichloropyridine, a tetrachloropyridine or pentachloropyridine with zinc metal, in the presence of an acidic compound and at a temperature in the range 50-120° C.

This application is a 371 of PCT/GB00/02613, filed Jul. 7, 2000.

The present invention concerns a process for the preparation of3,5-dichloropyridine. 3,5-Dichloropyridine is used as an intermediate inthe chemical industry (especially in the agrochemical industry).

The present invention provides a process for the preparation of3,5-dichloropyridine comprising reacting a trichloropyridine, atetrachloropyridine or pentachloropyridine with zinc metal, in thepresence of an acidic compound and at a temperature in the range 50-120°C.

Trichloropyridines include 2,3,5-trichloropyridine. Tetrachloropyridineis 2,3,4,5- or 2,3,5,6-tetrachloropyridine.

It is preferred that the process of the present invention is conductedin the presence of a protic solvent, such as water or an alcohol (forexample sec-butanol). Also, the process of the present invention can beconducted in the presence of a mixture of solvents (such as a mixture ofwater and 1,4-dioxane).

Suitable acidic compounds include mineral acids (such as hydrochloricacid or sulphuric acid), organic acids (such as formic acid or aceticacid) or suitable ammonium salts (such as ammonium chloride).

In one aspect the present invention provides a process for preparing3,5-dichloropyridine comprising reacting 2,3,5-trichloropyridine withzinc metal, in the presence of an acidic compound and at a temperaturein the range 50-120° C.

In a further aspect the present invention provides a process forpreparing 3,5-dichloropyridine comprising:

a) reacting acrylonitrile with anhydrous chloral in the presence ofcopper (I) chloride (and preferably in the presence of a suitablesolvent (such as acetonitrile)) at a temperature in the range 100-200°C., to form 2,3,5-trichloropyridine; and,

b) reacting the 2,3,5-trichloropyridine so formed with zinc metal, inthe presence of an acidic compound and at a temperature in the range50-120° C.

In a still further aspect steps (a) and (b) are conducted withoutpurification of the intermediate 2,3,5-trichloropyridine.

In another aspect the present invention provides a process for thepreparation of 3,5-dichloropyridine comprising reacting2,3,4,5,6-pentachloropyridine with zinc metal, in the presence of anacidic compound and at a temperature in the range 80-120° C., wherein aquantity of 3,5-dichloropyridine (preferably sufficient so that, underthe process conditions, the melting point of2,3,4,5,6-pentachloropyridine is below 100° C. at the beginning of theprocess) is present at the beginning of the process.

The following Examples illustrate the invention.

EXAMPLE 1

This Example illustrates the preparation of 3,5-dichloropyridine from2,3,4,5,6-pentachloropyridine

Procedure 1

Water (45 ml) was charged to a round bottomed flask fitted withtemperature probe, a reflux condenser and an overhead stirrer (toprovide good agitation during the course of the reaction). Agitationcommenced and acetic acid (6 ml) was added followed by finely ground(mortar and pestle) 2,3,4,5,6-pentachloropyridine (10 g), then3,5dichloropyridine (4.0 g) and finally zinc metal (20 g). The resultingmixture was heated to 81-82° C. for a total of 30 hours. (From time totime the cooler parts of the flask were gently warmed to melt smallamounts of solid 3,5-dichloropyridine that had sublimed there.)

After 30 hours chromatography showed that all of the2,3,4,5,6-pentachloropyridine had been consumed and only small amountsof tri- or tetra- chloropyridines remained.

Water (10 ml) was added to the reaction mixture followed by concentratedhydrochloric acid (10 ml). More water (20 ml) was then added.

The reactor was rigged for steam distillation and heated. Distillate wascollected at a still head temperature of 98-100° C. Distillate wascollected for a further 30 minutes and the distillate was a colourlessoil plus water. (Further quantities of water were added during the steamdistillation.) The oil crystallised on cooling.

The total distillate was extracted with dichloromethane (2×50 ml), theextracts were combined. dried over sodium sulphate and evaporated underreduced pressure to give 3,5-dichloropyridine as a white, low meltingpoint solid (6.99 g, gas chromatography showed an 86.4 area % of3,5-dichloropyridine equivalent to a yield of 44.6% based on thepentachloropyridine charged).

¹H NMR showed a 2 proton doublet at 8.48 ppm, and 1 proton triplet at7.7 ppm.

Procedure 2

Water (45 ml) was charged to a round-bottomed flask fitted withtemperature probe, an overhead stirrer to provide good agitation duringthe course of the reaction and a reflux condenser. Agitation commenced,acetic acid (6 ml) and 1,4-dioxane (8 ml) were added followed by finelyground (mortar and pestle) 2,3,4,5,6-pentachloropyridine (10 g) then3,5-dichloropyridine (4.0 g) and finally zinc metal (20 g). The mixturewas heated to 81-82° C. for a total of 29 hours. Chromatographyconfirmed that all of the pentahloropyridine had been consumed withsmall amounts of intermediate tri- and tetra- chloropyridines remaining.

Water (10 ml) was added followed by concentrated hydrochloric acid (10ml) and prior to steam distillation a further quantity of water (20 ml)was added. The reactor was rigged for steam distillation and distillatewas collected at a still head temperature of 98-100° C. Distilate wascollected for a further 15 minutes to give a colourless oil plus water,the oil crystallising on cooling. (Further quantities of water wereadded during the steam distillation.)

The distillate was extracted with dichloromethane (2×50 ml), theextracts were combined, dried over sodium sulphate and evaporated underreduced pressure to give the title compound as a white low melting pointsolid (8.5 g, gas chromatography showed an 78 area% of3,5-dichloropyridine equivalent to a yield of 60.8% based on thepentachloropyridine charged).

Procedure 3

2,3,4,5,6-Pentachloropyridine (5 g) was stirred together with glacialacetic acid (45 ml) and sodium acetate (5.4 g), zinc metal dust (4.33 g)and the mixture the heated to 100° C. over 30 minutes. After 4 hours awhite precipitate had formed and analysis showed that 50% conversion hadoccurred. Further zinc dust (4.33 g) was added and stirring and heatingwere continued for a further hour after which time analysis showed thereaction to be complete.

Water (75 ml) was added and the reactor set for steam distilation.Distillate was collected at a head temp up to 101° C. and continueduntil the head temperature began to rise. The condenser was washedthrough with dichloromethane (25 ml) to dissolve the solid product thathad collected therein. The organic phase was then separated from theaqueous phase. The aqueous phase extracted twice with dichloromethane.The organic extracts were combined, dried over magnesium sulphate andevaporated under reduced pressure to give the title compound as a whitesolid (1.9 g, yield 65% on pentachloropyridine charged).

EXAMPLE 2

This Example illustrates the preparation of 3,5-dichloropyridine from2,3,5-trichloropyridine.

2,3,5-Trichloropyridine (3.6 g) was charged to a round bottomed flaskcontaining water (9.0 ml) and acetic acid (2.0 ml). The mixture wasagitated with a magnetic follower, zinc metal powder (2.5 g) added andthe mixture was heated to 95° C. The reaction was monitored bychromatography and after 1 hour all of the 2,3,5-trichloropyridine hadbeen consumed. The mixture was steam distilled to give water plus an oilthat solidified on cooling. The solid was dissolved in dichloromethane(20 ml), the organic phase was separated, dried by passage under gravitythrough a filter paper and evaporated under reduced pressure to give thetitle compound as a low melting point solid (2.51 g, yield of 87.3%).Material confirmed as 3,5-dichloropyridine by comparative chromatographyand ¹H NMR.

EXAMPLE 3

This Example illustrates the preparation of 3,5-dichloropyridine from2,3,5-trichloropyridine.

Step 1

Copper (I) chloride (100 mg) was charged to a glass Carrius™ tubetogether with acetonitrile (7.5 ml) and acrylonitrile (1 g) andanhydrous chloral (3.3 g). The mixture was heated to 120° C. for 16hours and allowed to cool to room temp whilst a small sample waswithdrawn for analysis. The reaction mixture was reheated for 3 hours at175° C. and then allowed to cool again. Chromatography confirmed thepresence of 2,3,5-trichloropyridine in the reaction mass.

Step 2

To approximately half the crude reaction mass from Step 1 was addedwater (15 ml), zinc metal powder (2.0 g) and acetic acid. The mixturewas heated to 65° C. After 2 hours 25 minutes a further quantity of zincmetal (0.5 g) was added and heating was continued for a further 2 hours50 minutes. The resulting mixture was steam distilled untilapproximately 8 mls of distillate had been collected. The addition ofwater (10 ml) to the distillate caused a white solid to precipitate. Theresulting distillate mixture was extracted with dichloromethane (20 ml)and the organic and inorganic phases were added to water (50 ml). Theorganic phase was separated and the aqueous phase re-extracted with afurther quantity of dichloromethane (20 ml). The organic extracts werecombined, washed with water (50 ml), dried over magnesium sulphate, thedrying agent was filtered off and washed with dichloromethane. Thefiltrate was evaporated under reduced pressure to give the titlecompound as a white solid (0.531 g, approximate yield of 42% based onacrylonitrile charged).

EXAMPLE 4

This Example illustrates the preparation of 3,5-dichloropyridine from2,3,4,5-tetrachloropyridine.

2,3,4,5-Tetrachloropyridine (1 g) was charged to a reaction tubecontaining water (2 ml), 1,4-dioxane (6 ml), ammonium chloride (0.8 g)and zinc powder (1.5 g). Agitation was commenced (magnetic follower) andthe reaction tube heated to 90-92° C. for 8 hours. Gas chromatography ofthe reaction mixture showed that it comprised a monochloropyridine 1.8%and 3,5-dichloropyridine 98%.

EXAMPLE 5

This Example illustrates the preparation of 3,5-dichloropyridine from2,3,5,6-tetrachloropyridine.

2,3,5,6-Tetrachloropyridine (1 g) was charged to a reaction tubecontaining water (2 ml), 1,4-dioxane (6 ml), ammonium chloride (0.8 g)and zinc powder (1.5 g). Agitation was commenced (magnetic follower) andthe reaction tube heated to 90-92° C. for 12 hours. Gas chromatographyof the reaction mixture showed that it comprised: 3,5-dichloropyridine77.8%, 2,3,5-trichloropyridine 7.7% and 2,3,5,6-terachloropyridine14.5%.

What is claimed is:
 1. A process for preparing 3,5-dichloropyridinecomprising: a) reacting acrylonitrile with anhydrous chloral in thepresence of copper (I) chloride at a temperature in the range 100-200°C., to form 2,3,5-trichloropyridine; and, b) reacting the2,3,5-trichloropyridine so formed with zinc metal, in the presence of anacidic compound and at a temperature in the range 50-120° C.
 2. Aprocess according to claim 1 in which steps (a) and (b) are conductedwithout purification of the intermediate 2,3,5-trichloropyridine.
 3. Aprocess according to claim 1 in which the reaction of step (a) isconducted in the presence of a suitable solvent.
 4. A process accordingto claim 3 in which the solvent is acetonitrile.